Clinical, genomic, and neurophysiological correlates of lifetime suicide attempts among individuals with an alcohol use disorder

Complex Psychiatry, Год журнала: 2025, Номер 11(1), С. 1 - 11

Опубликована: Фев. 13, 2025

Introduction: Research has identified multiple risk factors associated with suicide attempt (SA) among individuals psychiatric illness. However, there is limited research those an alcohol use disorder (AUD), despite their disproportionately higher rates of SA. Methods: We examined lifetime SA in 4,068 AUD from the Collaborative Study on Genetics Alcoholism (23% SA; 53% female; mean age: 38). explored for across other clinical conditions ascertained a interview, polygenic scores comorbid problems, and neurocognitive functioning. Results: Participants who attempted had greater trauma exposure, major depressive disorder, post-traumatic stress substance disorders (SUDs), suicidal ideation. Polygenic SA, depression, PTSD were increased odds reporting (ORs = 1.22–1.44). reported also decreased right hemispheric frontal-parietal theta interhemispheric temporal-parietal alpha electroencephalogram resting-state coherences relative to did not, but differences small. Conclusions: Overall, report experience levels trauma, have more severe comorbidities, carry problems. Our results demonstrate need further investigate SAs presence SUDs.

Язык: Английский

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The Collaborative Study on the Genetics of Alcoholism: Overview

Genes Brain & Behavior, Год журнала: 2023, Номер 22(5)

Опубликована: Сен. 22, 2023

Abstract Alcohol use disorders (AUD) are commonly occurring, heritable and polygenic with etiological origins in the brain environment. To outline causes consequences of alcohol‐related milestones, including AUD, their related psychiatric comorbidities, Collaborative Study on Genetics Alcoholism (COGA) was launched 1989 a gene‐brain‐behavior framework. COGA is family based, diverse (~25% self‐identified African American, ~52% female) sample, data 17,878 individuals, ages 7–97 years, 2246 families which proportion densely affected for AUD. All participants responded to questionnaires (e.g., personality) Semi‐Structured Assessment (SSAGA) gathers information diagnoses, conditions behaviors parental monitoring). In addition, 9871 individuals have function from electroencephalogram (EEG) recordings while 12,009 been genotyped genome‐wide association study (GWAS) arrays. A series functional genomics studies examine specific cellular molecular mechanisms underlying This overview provides framework development as scientific resource past three decades, individual reviews providing in‐depth descriptions discoveries behavioral clinical, function, genetic data. The value also resides its sharing policies, efforts communicate findings broader community via project website potential nurture early career investigators generate independent research that has broadened impact into

Язык: Английский

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Diagnostic Criteria for Identifying Individuals at High Risk of Progression From Mild or Moderate to Severe Alcohol Use Disorder

JAMA Network Open, Год журнала: 2023, Номер 6(10), С. e2337192 - e2337192

Опубликована: Окт. 10, 2023

Importance Current Diagnostic and Statistical Manual of Mental Disorders (Fifth Edition) ( DSM-5 ) diagnoses substance use disorders rely on criterion count–based approaches, disregarding severity grading indexed by individual criteria. Objective To examine correlates alcohol disorder (AUD) across count-based groups (ie, mild, moderate, mild-to-moderate, severe), identify specific diagnostic criteria indicative greater severity, evaluate whether within mild-to-moderate AUD differentiate relevant manifest in hazards severe development. Design, Setting, Participants This cohort study involved 2 cohorts from the family-based Collaborative Study Genetics Alcoholism (COGA) with 7 sites United States: cross-sectional (assessed 1991-2005) longitudinal 2004-2019). analyses were conducted December 2022 to June 2023. Main Outcomes Measures Sociodemographic, alcohol-related, psychiatric comorbidity, brain electroencephalography (EEG), polygenic score measures as levels severe) severity–defined low-risk vs high-risk mild-to-moderate). Results A total 13 110 individuals COGA (mean [SD] age, 37.8 [14.2] years) 2818 baseline 16.1 [3.2] included. Associations psychiatric, EEG, reinforced role increasing counts indexing severity. Yet (2-5 criteria), presence (eg, withdrawal) identified a group reporting heavier drinking comorbidity even after accounting for count differences. In analyses, prior characterized endorsement at least 1 was associated more accelerated progression (adjusted hazard ratio [aHR], 11.62; 95% CI, 7.54-17.92) compared without (aHR, 5.64; 3.28-9.70), independent count. Conclusions Relevance this combined 15 928 individuals, findings suggested that simple approaches estimating vulnerability, which ignore heterogeneity among criteria, may be improved emphasizing Such emphasis allow better focus greatest risk improve understanding development AUD.

Язык: Английский

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Whole Genome Sequencing of Pedigrees With High Density of Substance Use and Psychiatric Disorders: A Meeting Report

Genes Brain & Behavior, Год журнала: 2025, Номер 24(1)

Опубликована: Фев. 1, 2025

ABSTRACT The National Institute of Drug Abuse convened a panel scientists with expertise in substance use disorders (SUD) and genetic methodologies primarily to determine the feasibility performing whole genome sequencing utilizing existing pedigree collections high density SUD psychiatric disorders. A major focus was on determining if there had been any successes identifying variants for complex traits family‐based designs. Such information could provide assurance that might significant pay‐offs particularly pursuit rare copy number variants. An important goal discuss evaluate optimal strategies studying human samples. Specific topics were (a) consider whether smaller cases typically available family studies versus larger biobanks can reveal unique information; (b) identify potential gaps biobank data be supplemented data; (c) phenotypic definitions (e.g., quantity use, problem‐oriented) collection instruments (self‐report or clinician administered) are both practical efficient collect, likely insights concerning prevention, intervention, medication development. Conclusions reached by included optimism about have occurred ascertained include densely affected pedigrees. Evaluation led, overall, consensus steps should taken utilize conjunction investigations variant discovery.

Язык: Английский

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Alcohol use disorder and body mass index show genetic pleiotropy and shared neural associations

Nature Human Behaviour, Год журнала: 2025, Номер unknown

Опубликована: Март 31, 2025

Язык: Английский

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Non-linear development of EEG coherence in adolescents and young adults shown by the analysis of neurophysiological trajectories and their covariance

bioRxiv (Cold Spring Harbor Laboratory), Год журнала: 2024, Номер unknown

Опубликована: Март 14, 2024

Abstract To contribute to the understanding of changes in factors governing development neural connectivity, developmental structure EEG coherence adolescents and young adults was analyzed using means, variances, covariances high alpha frequency band measures from a set 27 pairs obtained sample 1426 participants COGA study with 5006 observations over ages 12 through 31. Means were calculated at 96 age centers by LOESS method. In current study, trajectories covariance matrices considered as individual units determined tensorial analysis: calculation Riemannian geodesic (non-Euclidean) distances between application both linear non-linear dimension reduction techniques these distances. Results evaluated bootstrap methods. Mean for males females very similar, showing steady upward trend 20 which diminishes gradually 25 reaches stability contrast, female differed, male levels becoming greater than that during process. Tensorial determination initial matrix subsequent had same trajectory mean values. based on their all revealed pattern multi-dimensional space each trajectories: A increase one is accompanied deviations it peaking have transient lasting effects. There precise temporal parallelism this females, while there consistent distance structures throughout Between region differences (anterior-posterior) within sex are regions. Examining multiple methods provides unique insight into

Язык: Английский

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Neurocognitive Latent Factors Associate With Early Tobacco and Alcohol Use Among Adolescent Brain Cognitive Development Study Youth

Journal of Adolescent Health, Год журнала: 2024, Номер 75(6), С. 874 - 882

Опубликована: Авг. 13, 2024

Язык: Английский

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Is working memory intact in alcoholics? An ERP study

Psychiatry Research Neuroimaging, Год журнала: 1997, Номер 75(2), С. 75 - 89

Опубликована: Сен. 1, 1997

Язык: Английский

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Specific diagnostic criteria identify those at high risk for progression from ‘preaddiction’ to severe alcohol use disorder

medRxiv (Cold Spring Harbor Laboratory), Год журнала: 2023, Номер unknown

Опубликована: Июнь 20, 2023

Abstract Importance Both current DSM-5 diagnoses of substance use disorders (SUDs) and the recent “preaddiction” conceptual proposal (i.e., mild-to-moderate SUD) rely on criterion count-based approaches, without consideration evidence regarding varying severity grading indexed by individual criteria. Objective To examine correlates alcohol disorder (AUD) across groups mild, moderate, mild-to-moderate, severe), identify specific diagnostic criteria indicative greater severity, evaluate whether presence within AUD differentiates relevant manifests in hazards severe development. Design Cross-sectional longitudinal cohort study. Setting Family-based study individuals from seven sites United States. Participants ( N =13,110; mean [SD] age, 37.8 [14.2] years) cohorts =2,818; baseline 16.1 [3.2] Collaborative Study Genetics Alcoholism (COGA). Exposure N/A Main Outcomes Measures Sociodemographic, alcohol-related, psychiatric comorbidity (major depressive disorder, antisocial personality other SUDs), brain electroencephalography (EEG), polygenic score measures as levels severe) severity-defined low-risk vs. high-risk mild-to-moderate) groups. Results Associations with psychiatric, EEG, reinforced role increasing counts indexing severity. Yet even those meeting for (2-5 criteria), “high-risk” (e.g., withdrawal) identified a group reporting heavier drinking after accounting count differences. In analyses, prior characterized endorsement at least one outperformed adolescent young adult progression comorbid diagnoses, involvement milestones) was associated more accelerated to (adjusted hazard ratio [aHR], 11.62; 95% CI, 7.54-17.92) compared (aHR, 5.64; 3.28-9.70), independent count. Conclusions Relevance Current approaches concept both ignore heterogeneity among Estimating addiction vulnerability emphasizing may improve our understanding its development focus attention greatest risk. Key Points Question Does emphasis identification risk developing AUD? Findings Individuals are two-fold likely progress if they endorse despite physical/psychological problems, giving up important activities, spending great deal time drinking, failure fulfill major obligations, withdrawal, craving, total Meaning Emphasis especially indicators increase detection likelihood progression.

Язык: Английский

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Polygenic Risk for Alcohol Use Disorder Affects Cellular Responses to Ethanol Exposure in a Human Microglial Cell Model

bioRxiv (Cold Spring Harbor Laboratory), Год журнала: 2024, Номер unknown

Опубликована: Фев. 21, 2024

Abstract Polygenic risk scores (PRS) assess genetic susceptibility to Alcohol Use Disorder (AUD), yet their molecular implications remain underexplored. Neuroimmune interactions, particularly in microglia, are recognized as significant contributors AUD pathophysiology. We investigated the interplay between PRS and ethanol human microglia derived from iPSCs individuals with high- or low-PRS (HPRS LPRS) of AUD. Ethanol exposure induced elevated CD68 expression morphological changes differential responses HPRS LPRS microglial cells. Transcriptomic analysis revealed differences MHCII complex phagocytosis-related genes following exposure; cells displayed enhanced phagocytosis increased CLEC7A expression, unlike Synapse numbers co-cultures neurons after alcohol were lower HRPS co-cultures, suggesting possible excess synapse pruning. This study provides insights into intricate relationship PRS, ethanol, function, potentially influencing neuronal functions developing

Язык: Английский

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